The term “Chemotherapy” refers to treatment with a chemical agent. Chemotherapy can be defined as the utilization of pharmaceuticals specifically designed to target, combat and destroy diseased cells, according to the American Cancer Society.
Chemotherapy is one of the methods of treatment for Cancers, Autoimmune diseases such as Systemic sclerosis, Lupus Erythematosus , Rheumatoid Arthritis, Vasculitis and certain viral infections.
In case of cancer, the chemotherapeutic agent destroys cancer cells by targeting rapidly dividing cells in the body. Due to lack of specificity to cancer cells, the toxic effects of chemotherapy are also seen in other rapidly dividing non-cancerous cells. Blood cells, cells in the mouth, intestinal tract, nose, nails and hair are some of the rapidly dividing cells in the body. Destruction of normal cells in the body gives rise to side effects like alopecia, cachexia, anemia, leucopenia, neutropenia etc. These side effects limit the effectiveness of chemotherapy and increase risk of dose reduction, which directly impacts a patient's chances of survival against cancer.
In case of autoimmune diseases, Cyclophosphamide (CPM) has been used in Systemic sclerosis (Patricia Andrade de Macedo, 2009). It is an immunosuppressive alkylating agent which suppresses and modulates lymphocytes by means of the modification of cellular components.
Complete hair loss is an unusual complication of CPM in the doses typically used to treat Vasculitis. More commonly, mild to moderate thinning of the hair occurs.
In viral infections, Interferon alfa-2b acts as biological response modifier used in the treatment of Venereal warts, Hepatitis B, Chronic Hepatitis C and AIDS-related Kaposi's Sarcoma. Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens such as viruses, bacteria, parasites or tumor cells.
Interferon alfa-2b also acts as an antineoplastic agent in the treatment of Hairy Cell Leukemia, Melanoma and Mycosis Fungoides. Cachexia and Alopecia are two of the many side effects of this drug.
Cachexia or weight loss is a predominant side effect seen in all patients undergoing chemotherapy treatment. Cachexia is described as a syndrome of progressive weight loss, reduction in food intake, and persistent erosion of host body cell mass in response to a malignant growth. This condition is further worsened by chemotherapy. Chemotherapy treatment comprising anthracyclines, aromatase inhibitors, bleomycins, cytotoxic nucleosides, discodermolides, diynenes, epothilones, mitomycins, podophyllotoxins, pteridines, taxanes, vinca alkaloids etc., induce cachexia and fatigue in patients. Currently, there are no drugs which can prevent or treat chemotherapy induced cachexia. Parenteral nutritional support along with manipulation of host metabolism using insulin therapy or exercise can help in maintaining body weight. However, these methods do not prevent cachexia induced by chemotherapy.
Hair loss or Alopecia is yet another major side effect of chemotherapy. It is considered to be one of the most traumatic factors amongst patients undergoing chemotherapy, since it negatively impacts an individual's perception of appearance, body image and self-esteem. Hair loss or alopecia in patients undergoing chemotherapy is caused by toxic effects of chemotherapy on rapidly dividing cells that arrest mitotic activity in the hair follicles and influence hair shedding. It is mostly a reversible condition and limited to the duration of the chemotherapy treatment cycles.
The extent of hair loss depends on the type of chemotherapy used. Chemotherapy treatment comprising actinomycin-D, cyclophosphamide, bleomycin, daunorubicin, doxorubicin, epirubicin, irinotecan, paclitaxel, docetaxel, topotecan, vindesine etc., causes complete alopecia. Relatively less severe hair loss is seen with chemotherapy drugs like amsacrine, bleomycin, busulphan, capecitabine eribulin, etoposide, fludarabine, fluorouracil, gemcitabine, ifosfamide, lomustine, melphalan, mitoxantrone, thiotepa, vincristine, vinblastine, vinca alkaloids, vinorelbine etc. Drugs like cisplatin, carboplatin, carmustine, cytarabine, mercaptopurine, methotrexate, mitomycin, procarbazine, raltitrexate, sreptozotocin etc., rarely cause hair loss. However many of them cause thinning of hair along with change in color and texture of hair. Chemotherapy treatment comprises a cocktail of these drugs and nearly 65% of patients undergoing chemotherapy treatment experience alopecia.
At present, no approved pharmacological intervention exists to circumvent chemotherapy induced hair loss. Scalp cooling is practised as a major approach to minimize hair loss in patients undergoing chemotherapy. But the hypothermia causes uncomfortable chillness and headaches in patients. Topical application of drugs like Minoxidil and Finasteride can reduce the severity or shorten the duration of hair loss.
However, these drugs are developed for androgenic alopecia and their efficacy varies drastically in chemotherapy induced alopecia.
With the increasing number of patients undergoing chemotherapy, there is a need for interventions which can prevent or minimize these unaddressed side effects of chemotherapy. Most of the patients undergoing chemotherapy experience these side effects. The occurrence of these side effects of Chemotherapy depends upon the dose, route of administration and cytotoxicity of individual drug, combination of drugs, and other individual characteristics. For example, the anti-cancer drug Cyclophosphamide is widely used along with any other drug in combination in Lymphomas, Lung Cancer, Hodgkin's lymphoma, Non-Hodgkin's lymphoma as well as for autoimmune diseases such as Vasculitis. The drugs used in for chemotherapy treatment are generally cytotoxic in nature and therefore eliminate fast cells such as hair follicles.
Androgenic Alopecia (normal hair loss) and Anagen Effluvium (Chemo induced hair loss) are placed under different categories according to the ICD (International Classification of Diseases). Drugs like Minodixil work on normal hair loss but fail in the treatment of chemo induced hair loss. The instant invention is not related to hair growth. It works for the treatment of hair loss caused due to chemotherapy.
Hence, the present invention addresses these issues and provides a method of management of chemotherapy induced side effects namely cachexia and alopecia using a composition comprising pentameric type A procyanidin, trimeric procyanidin and tetrameric procyanidin, optionally along with pharmaceutical excipient to a subject in need thereof
Bhaskaran et al. (U.S. 2011/0039923 A1) discloses a composition comprising pentameric procyanidin flavonoid of concentration ranging from about 55% w/w to about 99% w/w, trimers and tetramers each at a concentration ranging from about 0.5% w/w to about 35% w/w. This document also discloses a process for preparation of the said composition from plant sources namely Cinnamon, Litchi and Arachis. Further, this document teaches use of the said composition for treatment and management of infections like HIV, AIDS and Influenza virus. However, this document does not suggest or teach the use of the said composition in prevention and management of chemotherapy induced cachexia and alopecia.